Evidence map›Paper›PMID 35086952›Full record

ArticleMolecular cancer therapeutics2022

89Zr-ImmunoPET Shows Therapeutic Efficacy of Anti-CD20-IFNα Fusion Protein in a Murine B-cell Lymphoma Model.

Kirstin A Zettlitz, Felix B Salazar, Reiko E Yamada, K Ryan Trinh, Alex Vasuthasawat, John M Timmerman, Sherie L Morrison, Anna M Wu

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Ultra-low dose immunoPET usingFrontiers in medicine · 2025
    Article
  5. European journal of nuclear medicine and molecular imaging · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Kirstin A ZettlitzCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0003-4870-6603
Felix B SalazarCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Reiko E YamadaDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0002-2680-6972
K Ryan TrinhDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
Alex VasuthasawatDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
John M TimmermanDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Sherie L MorrisonDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
Anna M WuCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0001-8487-823X
University of California, Los Angeles · USInstitute for Molecular Medicine · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Antibody-interferon fusion proteins for treatment of B-cell malignanciesR01CA162964 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MORRISON, SHERIE L · 2011 to 2015
$1.6M
Antibody-CpG conjugates for the treatment of B cell lymphomaR01CA149254 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIMMERMAN, JOHN M · 2010 to 2014
$1.5M
NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA149254NCI NIH HHS R01 CA162964
6 · The paper itself

Abstract

Antibody-mediated tumor delivery of cytokines can overcome limitations of systemic administration (toxicity, short half-lives). Previous work showed improved antitumor potency of anti-CD20-IFNα fusion proteins in preclinical mouse models of B-cell lymphoma. Although tumor targeting is mediated by the antibody part of the fusion protein, the cytokine component might strongly influence biodistribution and pharmacokinetics, as a result of its affinity, size, valency, and receptor distribution. Here, we used immunoPET to study the in vivo biodistribution and tumor targeting of the anti-CD20 rituximab-murine IFNα1 fusion protein (Rit-mIFNα) and compared it with the parental mAb (rituximab, Rit). Rit-mIFNα and Rit were radiolabeled with zirconium-89 (89Zr, t1/2 78.4 hours) and injected into C3H mice bearing syngeneic B-cell lymphomas (38C13-hCD20). Dynamic [(2 hours post injection (p.i.)] and static (4, 24, and 72 hours) PET scans were acquired. Ex vivo biodistribution was performed after the final scan. Both 89Zr-Rit-mIFNα and 89Zr-Rit specifically target hCD20-expressing B-cell lymphoma in vivo. 89Zr-Rit-mIFNα showed specific uptake in tumors (7.6 ± 1.0 %ID/g at 75 hours p.i.), which was significantly lower than 89Zr-Rit (38.4 ± 9.9 %ID/g, P < 0.0001). ImmunoPET studies also revealed differences in the biodistribution, 89Zr-Rit-mIFNα showed rapid blood clearance and high accumulation in the liver compared with 89Zr-Rit. Importantly, immunoPET clearly revealed a therapeutic effect of the single 89Zr-Rit-mIFNα dose, resulting in smaller tumors and fewer lymph node metastases compared with mice receiving 89Zr-Rit. Mice receiving 89Zr-Rit-mIFNα had enlarged spleens, suggesting that systemic immune activation contributes to therapeutic efficacy in addition to the direct antitumoral activity of IFNα. In conclusion, immunoPET allows the noninvasive tracking and quantification of the antibody-cytokine fusion protein and helps understand the in vivo behavior and therapeutic efficacy.

Indexed as

Lymphoma, B-CellRadioisotopesAnimalsCell Line, TumorHumansMiceMice, Inbred C3HPositron-Emission TomographyTissue DistributionZirconiumRadioisotopesZirconiumZirconium-89

Identifiers

PMID35086952
PMCPMC8983440
OpenAlexW4210408426

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.